Neuropeptide FF was originally identified as a mammalian counterpart of the molluscan cardioactive peptide FMRF-amide (Yang et al., 1985), found in the superficial dorsal horn of the spinal cord, hypothalamus, medulla and pituitary gland (Kivipelto et al. 1989). The findings that the peptide is present in the hypothalamo-pituitary system, decreases during salt-loading and is deficient in the pituitary gland of vasopressin-deficient Brattleboro rats, implicate NPFF involvement in hypothalamic regulation of pituitary functions (Majane and Yang, 1991; Majane and Yang, 1990; Majane et al., 1993). Peripherally administered NPFF raises blood pressure in rats, an effect mediated by both peripheral and central mechanisms (Allard et al., 1995; Laguzi et al., 1996). NPFF has also been implicated in sensory systems, most notably pain and morphine analgesia (Yang et al., 1985). Intracerebroventricular NPFF has been reported to induce a vigorous abstinence syndrome in morphine-tolerant rats. NPFF has attenuated the antinociceptive effects of morphine when administered in the third ventricle, whereas intrathecal NPFF produces long-lasting antinociception (Gouarderes et al., 1993).
The NPFF gene is located in the human chromosome locus 12q13 (Burke et al. 1998), which is known to be associated with a severe condition referred to as Allgrove syndrome (triple-A syndrome). The current NPFF promoter area is an evident region where mutations responsible for triple A syndrome are located. It serves as a useful marker for the appropriate area of chromosome 12, and has diagnostic and therapeutical value in treatment of a triple-A syndrome.